Siddhartha Yadav

Comparison of accuracy of physical examination findings in initial progress notes between paper charts and a newly implemented electronic health record.

Introduction: There have been several concerns about the quality of documentation in electronic health records (EHRs) when compared to paper charts. This study compares the accuracy of physical examination findings documentation between the two in initial progress notes. Methodology: Initial progress notes from patients with 5 specific diagnoses with invariable physical findings admitted to Beaumont Hospital, Royal Oak, between August 2011 and July 2013 were randomly selected for this study. A total of 500 progress notes were retrospectively reviewed. The paper chart arm consisted of progress notes completed prior to the transition to an EHR on July 1, 2012. The remaining charts were placed in the EHR arm. The primary endpoints were accuracy, inaccuracy, and omission of information. Secondary endpoints were time of initiation of progress note, word count, number of systems documented, and accuracy based on level of training. Results: The rate of inaccurate documentation was significantly higher in the EHRs compared to the paper charts (24.4% vs 4.4%). However, expected physical examination findings were more likely to be omitted in the paper notes compared to EHRs (41.2% vs 17.6%). Resident physicians had a smaller number of inaccuracies (5.3% vs 17.3%) and omissions (16.8% vs 33.9%) compared to attending physicians. Conclusions: During the initial phase of implementation of an EHR, inaccuracies were more common in progress notes in the EHR compared to the paper charts. Residents had a lower rate of inaccuracies and omissions compared to attending physicians. Further research is needed to identify training methods and incentives that can reduce inaccuracies in EHRs during initial implementation.

Outcomes of retesting BRCA-negative patients using multigene panels.

23 Background: New technologies for identifying hereditary predisposition to breast cancer have led to the discovery of novel genes associated with cancer risk. This has prompted re-evaluation of patients who previously tested negative for BRCA1/2 gene mutations, with a possibility of discovering new genes which may impact management. This study reports on the results of retesting patients who previously were negative for BRCA1/2. METHODS Patients who tested negative for BRCA1/2 mutations who had significant personal and family history were referred back to the Cancer Genetics Center between February 1, 2012 and May 30, 2105 for discussion of additional testing. A detailed personal and family history was reviewed, and patients were counseled about the genetics and clinical implications of panel testing for multiple breast cancer genes. Panel testing using next generation sequencing technologies was ordered. Patients were seen in follow up for discussion of results and management. RESULTS A total of 12 pathogenic mutations were identified during the study period. The genes and frequencies of these mutations were: CHEK2(3), PALB2(3), ATM(2), APC(1), BARD(1), CDH(1), MUTYH(1). There were 33 variants of undetermined significance(VUS) in 27 patients. 5 of these were seen in patients with a known pathogenic mutation; 3 others were later classified as benign. The frequencies of these VUSs were: ATM (9), PALB2(3), BARD1 (3), PTEN(3), PMS2(3), MSH6(2), CHEK2 (1), MYH(1), RAD51(1), BRIP1(2), NF1(1), BMPR1A(1). Of the 46 patients who had their initial BRCA testing and repeat panel testing between February 1, 2012 and May 30, 2015, 6 (13%) tested positive for a pathogenic mutation. CONCLUSIONS This study demonstrates the feasibility and potential clinical benefit of retesting individuals who previously tested negative for BRCA1/2 mutation. This approach had a significant management impact on patients and their families, with a 13% detection rate of pathogenic mutations. The success of retesting is predicated upon an infrastructure of provider and patient education, pre and post genetic counseling and serves as a model for other centers.

Comparison of Demographics, Tumor Characteristics, and Survival Between Pancreatic Adenocarcinomas and Pancreatic Neuroendocrine Tumors: A Population-based Study.

Objective: The objective of this study is to compare the incidence, demographics, tumor characteristics, and survival between patients with pancreatic neuroendocrine tumors (PNETs) and pancreatic adenocarcinomas. Materials and Methods: Between 2004 and 2012, all cases of pancreatic adenocarcinomas and PNETs were extracted from the population-based cancer registries of the Surveillance Epidemiology and End Results program. To identify the cases, a combination of topographical and histology codes based on ICD-O-3 were used. Incidence, demographics, tumor characteristics, and survival was then compared between these 2 histologic subtypes of pancreatic cancer. Results: A total of 57,688 patients with pancreatic cancer were identified, of which 53,753 (93%) had pancreatic adenocarcinoma and 3935 (7%) had PNET. The overall age-adjusted incidence of PNETs between 2004 and 2012 was 0.52 per 100,000 per year, whereas that for pancreatic adenocarcinomas during the same period was 7.34 per 100,000 per year. PNETs had a significantly younger median age at diagnosis (61 vs. 69 y). A significant proportion of PNETs were diagnosed at stage I (20.5% vs. 6.0%) and were well differentiated (32.8% vs. 4.5%) compared with adenocarcinomas. Five-year cause-specific survival was 51.3% and 5.0% for PNETs and pancreatic adenocarcinomas, respectively. In multivariate analysis, pancreatic adenocarcinomas had a hazard ratio for death of 4.02 (95% confidence interval, 3.79-4.28) when compared with PNETs. Conclusions: PNETs present with favorable features such as higher proportion of early-stage tumor, higher proportion of well differentiated tumors, and younger age at diagnosis. PNETs have a significantly better survival than pancreatic adenocarcinomas even after adjusting for age, sex, race, site, grade, and stage.

Intravascular large B cell lymphoma presenting as cholecystitis: diagnostic challenges persist.

Dear Editor, Intravascular large B cell lymphoma (IVLBCL) is a rare type of extranodal B cell lymphoma characterized by the presence of neoplastic lymphocytes in the lumina of small vessels. Approximately 300 cases have been reported to date [1]. Although it is often referred to as the “great imitator” due to its ability to affect any organ system [2], involvement of the gallbladder is rare. An 83-year-old male with a past medical history of hypertension, diabetes mellitus, and coronary artery disease presented with fatigue, shortness of breath with exertion, and intermittent confusion of 1-week duration. Physical examination revealed right upper quadrant tenderness. The remainder of the physical examination did not reveal any significant abnormality. Laboratory investigations revealed bicytopenia (white blood cell count of 3.1×10 cells/L, hemoglobin of 10 g/dL, platelets of 175×10 cells/L) that progressively worsened and evolved into pancytopenia. Lactate dehydrogenase was 1, 806 U/L. Haptoglobin was normal. Review of the peripheral smear revealed normocytic–normochromic anemia and absolute lymphopenia. There were no electrolyte abnormalities. Liver function tests revealed an elevated alkaline phosphatase of 237 U/L, aspartate aminotransaminase of 311 U/L, and alanine aminotransaminase of 62 U/L. Total bilirubin was normal. Ferritin was 290 ng/mL. Ultrasound of the abdomen showed thickening of gallbladder wall. HIDA scan was normal. CT scan of the abdomen with intravenous contrast revealed evidence of gallbladder thickening, pericholecystic fluid collection, and probable small stones in the gallbladder neck. No enlarged lymph nodes were noted. MRCP was subsequently performed which revealed evidence of gallbladder thickening and mucosal hyperenhancement. These findings were consistent with cholecystitis. Despite institution of antibiotic therapy, the patient deteriorated clinically, and liver enzymes continued to trend upwards. A decision to perform cholecystectomy was made. An edematous gallbladder and congested liver were noted during laparascopic cholecystectomy. Histopathology of the resected gallbladder showed large atypical cells within the vasculature of the gallbladder wall (see Fig. 1). These cells were positive for CD5, CD10, CD20, CD79a, BCL-2, and BCL-6 (see Fig. 2). A small lymph node adjacent to the gallbladder was involved with similar atypical cells. However, in the absence of any other lymph node involvement, a diagnosis of IVLBCL was made. Bone marrow biopsy revealed the presence of many large atypical B cells in a pattern highly suggestive of marrow sinus infiltration (See Fig. 3). Hemophagocytosis was not seen. The patient could not be extubated postoperatively, developed severe metabolic acidosis, and died 3 days after the surgery. In retrospect, the presence of pancytopenia and elevated lactate dehydrogenase in our patient pointed away from the diagnosis of a simple cholecystitis. These are the most common laboratory abnormalities seen in IVLBCL [3]. However, the nonspecificity of these tests makes it very difficult to suspect IVLBCL based on these laboratory parameters alone. S. Yadav (*) : L. Rosenbaum :M. A. Barnes Department of Internal Medicine, Beaumont Health System, 3601W 13 Mile Rd, Royal Oak, MI 48073, USA e-mail: sid.siddhartha@gmail.com

Renal cell carcinoma metastasis to the thyroid: how long is long enough?

Eribulin has been approved as treatment for patients with metastatic breast cancer, who have received at least two chemotherapeutic regimens including an anthracyclineand a taxane-based. When comparing the effects seen in the EMBRACE study with our results, very similar effects are found, with a medium progression-free survival time of 3.7 months in the EMBRACE study and 3.4 months in our sample. Concerning the clinical benefi t rate we even observed a slightly higher rate of 50% compared to the 23% reported in the EMBRACE trial. Adverse events occurred in 99% of the patients in the EMBRACE study compared to 87.5% in our sample. The most common adverse event in the EMBRACE study as well as in our study was fatigue. In the EMBRACE study the most common grade 3 and 4 adverse event was neutropenia. We also found neutropenia to have one of the highest incidences of grade 3 and 4 adverse events along with fatigue and peripheral neuropathy. Unfortunately, no registration of the preexisting neuropathy from previous treatment with other taxane-based chemotherapy regimens was performed. In conclusion we saw a side effect profi le very consistent to what we expected from prior studies. With the effect and side effect profi le of eribulin seen in this study, which is quite comparable to what is found in previous trials, it is worthwhile considering eribulin as a new standard of care. Additional considerations about when to introduce eribulin and who will benefi t the most from it need to be made.

Surgical decisions of newly diagnosed breast cancer patients following genetic referral.

40 Background: In response to many recent publications and mandates to assure referrals to genetic counseling for oncology patients, the Royal Oak (RO) Breast Care Center (BCC) at Beaumont Health System (BHS) evaluated the surgical outcomes of genetic referral(GR) in breast cancer (BC) patients. The goal of this study was to determine the impact of GR on surgical decision making and evaluate outcomes in this population. METHODS A retrospective chart review was performed, to identify patients who had a BC diagnosis and met criteria for GR from July 2012- July 2014. Age, histology, laterality of cancer, prior history of cancer, neoadjuvant chemotherapy, plastic surgery consultation, MRI, reason for MRI, additional testing, type of surgery, laterality of surgery, reconstruction, lymph node surgery, and time from diagnosis to surgery were evaluated using Chi Square analysis. RESULTS A total of 506 patients with a new BC diagnosis seen at the RO BCC at BHS within the inclusion dates were analyzed. There were 191 patients referred to the GP for counseling and possible genetic testing. Eighty percent of the referred patients underwent genetic testing. Twelve patients tested positive for deleterious mutations in BRCA 1 or 2. A statistically significant difference was found in the BC patients referred to the GP with respect to age, MRI usage, neoadjuvant chemotherapy, type and laterality of surgery, ALND, plastic surgery consult & reconstruction, and time from diagnosis to surgery. MRI usage in patients referred to GP was 43.5% vs. 12.7% in those not referred. Mastectomy rate in patients referred to GP was 51.3% vs. 25.5% (p<0.001) in those not referred. Bilateral mastectomy was 30.9% vs. 5.8% (p<0.001). CONCLUSIONS We have found that patients referred to the GP have increased the use of MRI testing, which in itself has been shown to increase mastectomy rates. We also identified a trend in these patients toward bilateral mastectomy. According to our outcomes, there are multiple possible reasons for this trend, including family history, physician bias, stage at diagnosis, age and factors intrinsic to the patient. Furthermore, a multivariate analysis is needed to assess the relationship between a GR and a patients surgical decision.

Abstract P4-12-13: Experience of pre-operative genetic testing on surgical decision making in newly diagnosed breast cancer patients

Introduction: BRCA 1 and 2 testing has been widely incorporated into clinical care for women at risk for hereditary breast cancer. Knowledge of BRCA mutation status prior to surgery may influence decision regarding type of surgery. This study analyzes the experience with pre-operative BRCA mutation testing in patients with suspected hereditary predisposition to breast cancer. Methodology: Records of 150 patients referred to Cancer Genetics between November 01, 2013 and April 30, 2014 for pre-operative genetic testing were analyzed. This cohort consisted of patients with newly diagnosed breast cancer who met current genetic testing criteria. Patients were excluded if their surgical records were not available or they had not yet completed surgery. A total of 80 patients who completed genetic evaluation and definitive surgery were evaluated. Data on demographic characteristics, tumor pathology, BRCA mutation status and surgical management was collected on all evaluable patients. Results: Records of 80 patients who underwent pre-operative genetic testing for hereditary breast cancer risk were evaluated. The median age at diagnosis was 51.5 years. Median time from biopsy to initiation of genetics referral was 10 days. From that point, the median time to cancer genetics appointment was 3 days. Median time from initial genetics visit to definitive surgery was 24 days. 7 (9%) patients underwent surgery within 10 days of the genetics appointment, and prior to receiving the results of the genetic tests. Of the 80 patients, 5 (6%) tested positive for a BRCA mutation, 3(4%) had a BRCA variant of unknown significance(VUS), and the rest tested negative. 4 of the 5 BRCA mutation carriers underwent bilateral mastectomy, as did 2 of the 3 patients with a BRCA VUS. Of the 72 BRCA -ve patients, 22 (30%) underwent bilateral mastectomies, 42 (58%) underwent partial mastectomy, 7 (10%) patients underwent unilateral mastectomy, and 1 underwent bilateral partial mastectomy. There was no significant difference on univariate analysis in the age, histopathology (grade, receptor status, lymph node status and margins) in the patients who underwent bilateral mastectomy and those who underwent breast conservation. Mean tumor size was 24.5 mm in the bilateral mastectomy group, compared to 15.8 mm in the unilateral mastectomy group(p=NS). The bilateral mastectomy group had a greater number of close relatives with breast cancer reflecting a more significant family history. Conclusions: This study demonstrates the feasibility and successful implementation of preoperative genetic testing in newly diagnosed breast cancer patients. The majority of mutation carriers underwent bilateral mastectomies as did a significant proportion of BRCA -ve patients. Larger tumor size and a more significant family history of breast cancer appeared to be associated with the decision to pursue bilateral mastectomy. Further studies are needed to better characterize the impact of preoperative genetic testing in newly diagnosed breast cancer patients. Citation Format: Siddhartha Yadav, Otavio Pereira-Rodrigues, Lindsay Dohany, Heidi Dreyfuss, Jennifer Fulbright, Ashley Reeves, Dana Zakalik. Experience of pre-operative genetic testing on surgical decision making in newly diagnosed breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-12-13.

Outcomes of patients with triple-negative breast cancer treated with radiation therapy.

88 Background: This study compares outcomes between different types of loco-regional treatment modalities used in patients with triple negative breast cancers. METHODS 299 patients with triple negative breast cancer diagnosed between April 2004 and August 2011 at a single institution and who were treated with radiation therapy were included in an IRB-approved retrospective review. Electronic charts were reviewed for demographic and pathologic data as well as outcome data including locoregional and distant recurrence. The median follow up period was 3 years. 200 (70%) patients underwent lumpectomy with whole breast irradiation (WBI). 68 (22.7%) patients received mastectomy and radiation while 31(10.4%) patients were treated with lumpectomy with accelerated partial breast irradiation (APBI). RESULTS Forty-nine patients (16.4%) experienced recurrence (10 local; 6 contralateral; 3 regional; 36 distant). There was a significant (p<0.0001) difference in the proportion of patients that experienced a recurrence in each treatment group: 34% (n=23) in mastectomy with radiation group; 12% (n=23) in lumpectomy with WBI group; 10% (n=3) in lumpectomy with APBI group. On univariate analysis, tumor size, tumor stage, nodal stage, overall stage, total number of positive nodes, total number of nodes removed, and whether or not the patients had an axillary lymph node dissection were significantly associated with recurrence (p<0.05). When these predictor variables, including treatment type, were examined using a stepwise cox proportional hazards regression model for recurrence, the only variables that remained significant were tumor stage (p= 0.0003) and the number of positive nodes (p= 0.0008). Survival curves were significantly different (p = 0.016) between the lumpectomy with WBI group and the mastectomy with radiation group. Over all follow-up times, the probability of survival was smallest for the mastectomy with radiation group. CONCLUSIONS The recurrence pattern for triple negative breast cancers treated with radiation therapy was primarily distant for all treatment modalities. In our patient population, tumor stage and number of positive lymph nodes predicted for recurrence while radiotherapy technique did not.

Abstract P2-09-06: Multi-gene panel testing for hereditary cancer risk

Background: Multi-gene panels are widely available for assessing hereditary cancer risk in high risk individuals. Due to the use of these panels, many genetic mutations other than BRCA 1 or 2 can be detected which can potentially affect management. This study presents the results of multi-gene panel testing performed at Beaumont Health System. Methods:All patients who underwent multi-gene panel testing at Beaumont Health System between November 1, 2012 and January 15, 2015 were included in this study. This cohort consisted of patients who met criteria for genetic testing due to personal or family history. All patients received comprehensive pre and post-test genetic counseling. The panels ranged from 5 to 43 genes associated with risk for breast and other cancers. Results: 653 multi-gene panel tests were performed. The majority of these consisted of either a 5 gene high risk breast panel (25%), an 18 gene moderate to high risk breast panel (21%), or a 9 gene high risk breast and gynecologic panel (17%). 184 variants of undetermined significance (VUS) were identified with a pooled VUS rate of 28%. Among the commonly used panels, there was a positive correlation between VUS rate and the number of genes included in the panel (r = 0.86, p = 0.01, Range 6% to 70%). A pathogenic mutation was identified in one or more genes in 65 (10%) panels for a total of 67 mutations. Of these, 17 mutations were in BRCA1 or BRCA2 gene. Fifty non-BRCA deleterious mutations were identified with the following frequencies: CHEK2(12), MUTYH(7 monoallelic, 1 biallelic), TP53(4), PTEN(4), ATM(4), MSH6(3), PALB2(3), MSH2(2), CDH1(2), APC(2), NF1(2), BARD1(2), MLH1(1) and PMS2(1). Of these non-BRCA mutations, 41(82%) had a significant impact on management. Conclusions: Our study demonstrates that multi-gene panel testing identifies several genes that can impact management and would likely not have been discovered by pedigree analysis alone. However, this added detection is associated with a higher VUS rate, especially using larger panels. Further research is needed to better define the role of multi-gene panel testing in high risk patients, with a focus on choosing appropriate genes, understanding the magnitude of cancer risk and delineating impact on management. Citation Format: Yadav S, Ladkany R, Fulbright J, Dreyfuss H, Reeves A, Campian S, Thomas V, Zakalik D. Multi-gene panel testing for hereditary cancer risk. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-06.

Abstract 2760: Impact of race and age on choice of surgery in newly diagnosed breast cancer patients who tested negative for BRCA 1/2 mutation

Introduction: The benefit of bilateral mastectomies in breast cancer patients who test negative for a deleterious BRCA mutation has not been proven. In spite of this, a significant number of women with unilateral breast cancer who test negative for BRCA mutation choose bilateral mastectomies. We aimed to evaluate the role of age and race in such decision making. Methodology: Records of 323 patients referred to Cancer Genetics between January 01,2012 and June 30,2014 for pre-operative genetic evaluation were analyzed. This cohort consisted of patients with newly diagnosed breast cancer who met genetic testing criteria. Patients were excluded if their surgical records were not available, they declined genetic testing, they underwent surgery prior to their test results being available or they were positive for BRCA mutation. A total of 148 patients met our inclusion criteria and were evaluated for final analysis. Statistical analysis was performed using SPSS21. Results: Of the 148 women with breast cancer who tested negative for a deleterious BRCA mutation, 116(78%) were Caucasian, 9(6%) were African-American, 5(3%) were Asian, 4(3%) were Arab, 3(2%) were Indian, 2(2%) were American-Indian and 1(1%) was Hispanic. The race or ethnicity could not be identified in 8(5%) patients. A total of 47(32%) patients ultimately underwent bilateral mastectomies in this cohort. Of these, 40(27%) underwent bilateral mastectomies as their initial surgery while 7(5%) underwent bilateral mastectomies eventually after undergoing partial mastectomy or simple mastectomy initially. There was no statistically significant difference between the mean ages of the group that underwent bilateral mastectomy (48.9 yrs) and the group that underwent partial or simple mastectomy (49.1 yrs). All of the 8 patients with an unknown ethnicity underwent bilateral mastectomy. The rest of the mastectomies (39) were performed in Caucasian patients. None of the non-Caucasian patients underwent bilateral mastectomy. This difference was statistically significant (p Conclusion: Our study demonstrates that a significant proportion(32%) of BRCA negative women with breast cancer undergo bilateral mastectomies. Furthermore, Caucasian patients with BRCA negative breast cancer are more likely to choose bilateral mastectomies than non-Caucasians. However, this result has to be interpreted with caution as our sample size of non-Caucasians was small(24). Considering our catchment population, this small sample brings concerns that a significant proportion of non-Caucasian patients may not be undergoing genetic testing despite meeting criteria. We did not find a significant impact of age on choice of surgery in BRCA negative women with breast cancer. Further studies with larger sample size are needed to better understand the role of race and age in access to genetic testing and surgical decision making. Citation Format: Siddhartha Yadav, Heidi Dreyfuss, Jennifer Fulbright, Ashley Reeves, Sarah Campian, Dana Zakalik. Impact of race and age on choice of surgery in newly diagnosed breast cancer patients who tested negative for BRCA 1/2 mutation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2760. doi:10.1158/1538-7445.AM2015-2760